Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Clin Cancer Res. 2023 Nov 1;29(21):4408-4418. doi: 10.1158/1078-0432.CCR-23-1207.
We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR).
We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively. Tumor programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), next-generation sequencing (NGS), and whole-exome sequencing (WES) data were analyzed to identify characteristics enriched in patients achieving LTR compared with STR and non-LTR.
Among 3,118 patients, 8% achieved LTR and 7% achieved STR, with 5-year overall survival (OS) of 81% and 18% among LTR and STR patients, respectively. High TMB (≥50th percentile) enriched for LTR compared with STR (P = 0.001) and non-LTR (P < 0.001). Whereas PD-L1 ≥ 50% enriched for LTR compared with non-LTR (P < 0.001), PD-L1 ≥ 50% did not enrich for LTR compared with STR (P = 0.181). Nonsquamous histology (P = 0.040) and increasing depth of response [median best overall response (BOR) -65% vs. -46%, P < 0.001] also associated with LTR compared with STR; no individual genomic alterations were uniquely enriched among LTR patients.
Among patients with advanced NSCLC treated with ICIs, distinct features including high TMB, nonsquamous histology, and depth of radiographic improvement distinguish patients poised to achieve LTR compared with initial response followed by progression, whereas high PD-L1 does not.
我们旨在确定接受免疫检查点抑制剂（ICI）治疗的晚期非小细胞肺癌（NSCLC）患者中实现长期缓解（LTR）的患者的特征，以及这些特征如何与预测短期缓解（STR）的特征不同。
我们对 2011 年至 2022 年间接受 ICI 治疗的晚期 NSCLC 患者进行了多中心回顾性分析。LTR 和 STR 分别定义为缓解≥24 个月和缓解<12 个月。分析肿瘤程序性死亡配体 1（PD-L1）表达、肿瘤突变负荷（TMB）、下一代测序（NGS）和全外显子组测序（WES）数据，以确定与 STR 和非 LTR 相比，在实现 LTR 的患者中富集的特征。
在 3118 名患者中，8%达到 LTR，7%达到 STR，LTR 和 STR 患者的 5 年总生存率（OS）分别为 81%和 18%。高 TMB（≥50%分位数）与 STR（P=0.001）和非 LTR（P<0.001）相比，LTR 丰富。而 PD-L1≥50%与非 LTR 相比，LTR 丰富（P<0.001），但与 STR 相比，LTR 不丰富（P=0.181）。非鳞状组织学（P=0.040）和反应深度增加[中位最佳总体反应（BOR）-65%比-46%，P<0.001]也与 STR 相比与 LTR 相关；LTR 患者中没有独特的基因组改变富集。
在接受 ICI 治疗的晚期 NSCLC 患者中，包括高 TMB、非鳞状组织学和影像学改善程度在内的独特特征可区分有望实现 LTR 的患者与初始缓解后进展的患者，而高 PD-L1 则不然。
